Phase I/II study of stereotactic radiation and sacituzumab govitecan with zimberelimab in the management of metastatic triple negative breast cancer with brain metastases.

TPS1140 Background: Patients with triple negative breast cancer (TNBC) are at a high risk to develop brain metastases. The prognosis and quality of life for triple negative brain-metastatic breast cancer remains very poor. Treatment options are limited and improvement in efficacy is needed. Sacituzumab govitecan (SG) has shown blood brain barrier (BBB) penetration in preclinical and clinical settings with anti-tumor activity in the phase III ASCENT Trial (NCT02574455). Radiotherapy can open the BBB and has been shown to be safe in combination with anti-PD-1 therapy in our previous trial (NCT03807765). Therefore, combining radiation with the anti-PD-1 monoclonal antibody, zimberelimab, and SG may provide a synergistic anti-tumor approach. We hypothesize the use of SG and zimberelimab with stereotactic radiosurgery (SRS) among patients with metastatic TNBC with brain metastases will be safe and improve progression free survival compared to treatment with SG alone. Methods: The study is designed as a single-arm, nonrandomized, open-label, phase I/II trial of SG and zimberelimab with SRS among patients with metastatic TNBC with brain metastases. The primary endpoint will be neurologic toxicity defined by CTCAE v5 criteria (phase I) and 12 month PFS (phase II). TNBC patients ≥ 18 years old with ≤ 15 brain metastases with at least one measurable lesion ≥ 0.5 cm per RANO-BM criteria will be enrolled. Treatment will be initiated with SRS followed 1 week later by SG on days 1 and 8 (10 mg/kg) with zimberelimab on day 1 (360 mg IV) repeated every 3 weeks. Follow-up imaging response assessments will be conducted at q9 week intervals. An interim analysis will be performed after 21 patients are enrolled. An additional 10 patients will be enrolled if interim futility criteria are not met. Clinical trial information: NCT06238921 .